Radiation-associated Angiosarcoma Research Articles

Radiation‐associated sarcoma after breast cancer in a nationwide population: Increasing risk of angiosarcoma

Radiation‐associated sarcoma (RAS) is a rare complication of radiation therapy (RT) to breast cancer (BC). This study explored RAS after RT to BC in a nationwide population‐based material. The Finnish Cancer Registry was queried for patients with BC treated during 1953‐2014 who were later diagnosed with a secondary sarcoma in 1953‐2014. Registry data, patient files, and sarcoma specimens were analyzed to confirm diagnosis and location of RAS at or close to the RT target volume. A total of 132 512 patients were diagnosed with invasive BC during the study period. A subsequent sarcoma was diagnosed in 355 patients. After exclusion, 96 RAS were identified. Angiosarcoma (AS) was the most prevalent histology in 50 (52%) of 96 patients. However, the first radiation‐associated AS was diagnosed in a patient treated for BC with breast‐conserving surgery in 1984, and thereafter, the proportion of AS continuously increased. The 5‐year sarcoma‐specific survival was 75.1% for RAS treated with a curative intent. The distribution of histologic subtypes of RAS has changed during the 60 years of this registry study. The first radiation‐associated AS was diagnosed in 1989, and presently, AS is the most common histologic subtype of RAS. It is possible that changes in BC treatment strategies are influencing the characteristics of RAS.

Mutational landscape of radiation-associated angiosarcoma of the breast.

PurposeRadiation-associated breast angiosarcomas are a rare complication of radiation therapy for breast carcinoma. With relatively little is known about the genetic abnormalities present in these secondary tumors, we examined genomic variation in biospecimens from radiation-associated breast angiosarcomas.Experimental DesignPatients were identified that had a previous breast cancer diagnosis, received radiation therapy, and developed angiosarcoma in the ipsilateral breast as the earlier cancer. Tumor regions were isolated from archival blocks using subsequent laser capture microdissection. Next generation sequencing was performed using a targeted panel of 160 cancer-related genes. Genomic variants were identified for mutation and trinucleotide-based mutational signature analysis.Results44 variants in 34 genes were found in more than two thirds of the cases; this included 12 variants identified as potentially deleterious. Of particular note, the BRCA1 DNA damage response pathway was highly enriched with genetic variation. In a comparison to local recurrences, 14 variants in 11 genes were present in both the primary and recurrent lesions including variants in genes associated with the DNA damage response machinery. Furthermore, the mutational signature analysis shows that a previously defined IR signature is present in almost all of the current samples characterized by predominantly C→T substitutions.ConclusionsWhile radiation-associated breast angiosarcomas are relatively uncommon, their prognosis is very poor. These data demonstrate a mutational pattern associated with genes involved in DNA repair. While important in revealing the biology behind these tumors, it may also suggest new treatment strategies that will prove successful.

Clinical outcomes in breast angiosarcoma patients: A rare tumor with unique challenges.

Breast angiosarcoma (AS) accounts for less than 1% of all breast cancers. The goal of this study was to determine patient outcomes in radiation-associated angiosarcoma of the breast (RAAS) and sporadic AS. We evaluated patterns of recurrence and predictors of breast AS survival. Patients with pathologically confirmed AS from 1994 to 2014 referred to Mount Sinai Hospital/Princess Margaret Cancer Centre were included. Primary outcome was overall survival (OS). Secondary outcomes were disease-free survival (DFS), clinicopathologic characteristics, patterns of recurrence and factors predictive of survival. Kaplan-Meier and log-rank tests were used for OS and DFS. Twenty-six patients were included: 6 with sporadic AS and 20 with RAAS. Median follow-up was 24 months. Five-year OS for RAAS and sporadic subgroups were 44% and 40%, respectively (P = ns). Five-year DFS for RAAS and sporadic subgroups were 23% and 20%, respectively (P = ns). Overall recurrence rate was 67% with median time to recurrence of 11 months. Age, tumor depth, margin status, and tumor size were not statistically significant predictive factors for OS and DFS. Breast AS is associated with poor survival and high recurrence rates. Prognosis may be mainly determined by its aggressive biology. Referral to tertiary care centers for multimodality treatment is recommended.

Reduced H3K27me3 expression in radiation-associated angiosarcoma of the breast.

The diagnosis of radiation-associated angiosarcoma is challenging and there are overlapping clinicopathological features between radiation-associated benign, atypical and malignant vascular lesions. It has been shown convincingly, that the majority of radiation-associated angiosarcomas are characterised by amplification and subsequent overexpression of MYC in contrast to benign and atypical vascular lesions. Given the fact that epigenetic changes play an important role in carcinogenesis and loss of histone H3K27 trimethylation (H3K27me3) has been found in a number of malignant neoplasms including malignant peripheral nerve sheath tumours, especially when associated with previous radiotherapy, we evaluated the immunohistochemical reaction pattern for H3K27me3 in 49 vascular lesions and control cases: normal skin and benign vascular lesions not associated with previous radiotherapy, radiation-associated benign, atypical and malignant vascular lesions and angiosarcomas not associated with previous radiotherapy. We found loss of H3K27me3 expression in most cases of radiation-associated angiosarcomas, whereas endothelial cells in benign and atypical vascular lesions arising after previous radiotherapy stained positively for H3K27me3. The sporadic angiosarcomas stained inconsistently for H3K27me3. Loss of H3K27me3 is typically seen in radiation-associated angiosarcomas, representing an additional diagnostic tool and raises questions in regard to the carcinogenesis of malignant vascular neoplasms.

Differential Oncologic Outcome in Angiosarcoma by Anatomic Subsite and Association With Prior Radiation: Implications for Prognostication and Treatment Strategy

Angiosarcomas are rare, aggressive soft tissue sarcomas with a poor prognosis and a paucity of data to inform management decisions. Treatment typically consists of surgery and/or radiation or chemotherapy. We sought to characterize the impact of anatomic site of origin, prior radiation exposure, and treatment factors on clinical outcomes. We performed an IRB approved retrospective review of 181 patients with angiosarcoma treated at our institution between 1968 and 2015 and focused on 139 patients with localized disease. All of the cases were reviewed by central pathology. Overall survival (OS) and local control (LC) were estimated using the Kaplan-Meier method, together with multivariate analyses using the Cox proportional hazard regression model to identify prognostic factors. With a median follow up 24.1 months, the 2 year rates of OS and LC were 47.1% and 46.0%, respectively. The median OS was 30.3 months. 73 men and 66 women were treated with a median age of 68 years (range: 19 to 93 years). Site of primary included scalp (n=49, 35.3%), trunk (n=32, 23.0%), breast (n=28, 20.1%), extremity (n=26, 18.7%), and head and neck (n=4, 2.9%). Thirty-three (23.7%) patients had radiation-associated angiosarcomas (RAAS), including 15 patients with breast and 18 non-breast RAAS. Prior malignancies for RAAS included breast (n=22), prostate (n=2), rectal cancer (n=3), or other (n=6), with median time from prior malignancy to onset of RAAS of 7.5 years (range: 4 - 50). Patients were treated with surgery only (n=51, 36.7%), radiation (RT) only (n=19, 13.7%), or surgery with pre- and/or post-operative RT (n=63, 45.3%). 25.9% of the patients were treated with chemotherapy. On univariate and multivariate analysis, younger age (p<0.001), tumor size ≤ 5 cm (p<0.001), lower grade (p<0.05), surgery (p<0.001), and negative margins (p<0.001) were associated with improved OS. On multivariate analysis, LC was worse for patients with positive margins (HR 4.54, p<0.005) and also varied significantly depending on anatomic site of primary (p < 0.05). Radiation associated breast angiosarcoma had worse LC than spontaneous breast angiosarcoma with a 2-yr LC rate of 60.3% versus 82.3% (p<0.05) respectively though 2-yr OS of 70.0% versus 90.9% respectively was not statistically different. In our large single-institution retrospective experience with angiosarcoma, prognostic factors included age, tumor size, tumor grade, margin status, and surgical resectability. Local control was worse for radiation-related breast compared to spontaneous breast angiosarcoma, suggesting potential treatment or biologic differences that should be further investigated.

Radical chest wall resection and hyperfractionated accelerated radiotherapy for radiation-associated angiosarcoma of the breast: A safe and effective treatment strategy.

Radiation-associated angiosarcomas (RAS) of the breast are vascular tumors arising in a previous radiation field for primary breast cancer. They occur rarely but confer a high probability of local recurrence (LR) and poor prognosis. A wide range of treatment strategies exists due to limited evidence, and although resection is the definitive treatment, LR rates remain high. It has been suggested hyperfractionated accelerated radiotherapy (HART) has the potential to prevent LR. The sarcoma group at the Juravinski Cancer Centre (JCC) reports our experience of nine patients treated with radical resection and adjuvant HART. This is one of the largest reported cohorts we are aware of to receive this treatment. The JCC pathologic data base was reviewed between the year 2006-2015 for patients with RAS. Patients who received radical surgery and immediate HART were eligible. Patients underwent radical chest wall resection and en bloc mastectomy. Radiotherapy was then delivered to 4500 cGy in 45 fractions three times daily using parallel opposed photon beams and electron patching, or volumetric modulated arc therapy. Primary outcome was recurrence-free survival in months, and records were reviewed for descriptive reports of toxicity. We compared our results to other institutions experience with surgery alone or other adjuvant therapies. Median follow-up was 19 months (range 3-41 months). One of nine patients developed LR and developed metastasis, one died of other causes, and seven are alive with no recurrent disease. There were seven reports of mild skin toxicity during treatment. One patient developed chronic wound healing complications which eventually resolved and one patient developed asymptomatic radiation osteitis of a rib. On the basis of our experience at the JCC, we recommend treatment with radical chest wall resection and adjuvant HART to prevent recurrence in RAS patients. As demonstrated in our patients, the large normal tissue volume irradiated is tolerable with in combination with small fraction sizes, and no major toxicities were seen. Further investigation into adjuvant therapy regimens and prospective studies are required to reach consensus on optimal treatment for this disease.

Surgical management within a tertiary referral service leads to improved disease specific survival of patients with radiation-associated angiosarcoma of the breast

Surgical management within a tertiary referral service leads to improved disease specific survival of patients with radiation-associated angiosarcoma of the breast

MYC immunohistochemistry in angiosarcoma and atypical vascular lesions: practical considerations based on a single institutional experience

Angiosarcoma (AS) is an uncommon vascular malignancy with an aggressive clinical course. Radiation-associated angiosarcoma (RAAS) and Stewart-Treves syndrome are associated with MYC gene amplification and protein overexpression, while other radiation-associated vascular lesions including atypical vascular lesions (AVL) are not associated with MYC overexpression. In contrast, de novo AS represent a group of molecularly heterogeneous tumours, for which MYC expression has not been extensively examined. In this study, MYC immunohistochemistry (IHC) was performed on representative whole tissue sections of a large retrospective cohort of de novo AS, RAAS, Stewart-Treves syndrome, and AVL and evaluated using a semi-quantitative scoring method. MYC is strongly expressed in the majority of RAAS and Stewart-Treves syndrome. De novo AS demonstrate variable MYC expression, with high-grade tumours showing significantly higher MYC expression than low-grade tumours. In contrast, MYC expression in AVL is predominantly negative but may occasionally show focal staining. These results indicate that unequivocal strong MYC IHC staining supports the diagnosis of RAAS. In rare cases of RAAS without strong MYC expression, however, particularly relatively low-grade tumours for which the differential diagnosis includes AVL, the distinction between these lesions should be made on morphological grounds using previously established criteria (i.e., significant atypia, deep invasion, infiltrative growth, etc.). Increased MYC expression in high-grade de novo AS suggests that MYC overexpression may play a role in the pathogenesis of these tumours, and MYC IHC may be a prognostic and/or therapeutic biomarker in a subset of these tumours.

Su spinduliniu gydymu susijusi angiosarkoma po krūties vėžio gydymo: klinikinio atvejo aprašymas ir literatūros apžvalga

ĮžangaStraipsnio tikslas – aprašyti retą klinikinį su spinduliniu gydymu susijusį angiosarkomos atvejį po krūties tausojančios operacijos ir spindulinio vėžio gydymo, taip pat apžvelgti naujausius literatūros šaltinius.Klinikinis atvejisStraipsnyje aprašomas klinikinis 66 metų moters atvejis. Jai buvo diagnozuotas kairės krūties I stadijos vėžys (pT1cN0M0).2011 metais atlikta krūtį tausojanti operacija ir taikytas pooperacinės radioterapijos kursas (50 Gy). 2016 metais, po 5 metų nuo pirminio kairės krūties vėžio sudėtinio gydymo, šioje krūtyje nustatyta su spinduliniu gydymu susijusi angiosarkoma.Mes aptariame šios retos angiosarkomos klinikinį atvejį ir galimus gydymo metodus. Ligonė buvo gydoma Nacionaliniame vėžio institute.IšvadosAnkstyva diagnostika, daugiadalykis aptarimas, agresyvus R0 chirurginis gydymas ir adjuvantinio spindulinio gydymo dozės leidžia sėkmingiau gydyti šia retą patologinę būklę. Reikalingi papildomi moksliniai tyrimai, kurie padėtų nustatyti su spinduliniu gydymu susijusios angiosarkomos gydymo indikacijas.

Radiation-Associated Angiosarcoma of the Breast: Clinical and Pathologic Features.

Breast angiosarcoma is an unusual malignancy accounting for approximately 1% of soft tissue sarcomas. It can occur as a primary form without a known precursor or as a secondary form associated with radiotherapy. Adjuvant radiotherapy has a significant role in preventing local recurrence in women treated with conservation therapy for early stage breast carcinoma or multicentric tumors. Postradiation angiosarcoma usually affects the dermis of the breast within the radiation field and may occasionally develop in the breast parenchyma. Compared with the latency of other radiation-associated sarcomas, the latency for breast radiation-associated angiosarcoma is relatively short with a median of 6 years. The risk of developing secondary angiosarcoma does not outweigh the benefit of treatment; therefore, radiation therapy continues to be a mainstay modality in the treatment of breast cancer patients. Early detection is essential because angiosarcomas are associated with a poor prognosis. Wide surgical resection is the standard treatment for these tumors.

Radiation-Associated Angiosarcoma of the Breast: What the Radiologist Needs to Know.

The purpose of this article is to describe the diagnosis, treatment, and follow-up of radiation-associated angiosarcoma (RAS) of the breast. Radiologists play an important role in the diagnosis of RAS, which may initially present clinically as erythema, ecchymosis, or skin thickening. Conventional imaging with mammography and ultrasound is less sensitive than MRI for the diagnosis of RAS. Follow-up CT is important to monitor treatment response.

Advances in the clinicopathological and molecular classification of cutaneous mesenchymal neoplasms.

In recent years, there have been several important refinements in the classification of cutaneous mesenchymal neoplasms, including the description of new tumour types, along with the identification of novel and recurrent molecular genetic findings. In addition to providing new insights into tumour biology, many of these advances have had significant clinical consequences with regard to diagnostics, management, and prognostication. Newly described entities include pseudomyogenic haemangioendothelioma, haemosiderotic fibrolipomatous tumour, and fibroblastic connective tissue naevus, which are reviewed in the context of the principal differential diagnoses and significant clinical implications. Genetic characterization of several soft tissue tumour types that occur in the skin has resulted in the identification of diagnostically useful markers: ALK gene rearrangement with corresponding ALK protein expression by immunohistochemistry in epithelioid fibrous histiocytoma; the WWTR1-CAMTA1 fusion gene with CAMTA1 protein expression in epithelioid haemangioendothelioma; MYC amplification and overexpression in radiation-associated angiosarcoma; and EWSR1 gene rearrangement in cutaneous myoepithelial tumours. Finally, the classification of intradermal smooth muscle tumours and unclassified/pleomorphic dermal sarcoma has been refined, resulting in both improved classification and improved prognostication. Many of the tumour types listed above are encountered not only by specialist dermatopathologists, but also by practising general surgical pathologists, and this review should therefore provide a widely applicable update on the histological and molecular classification of cutaneous mesenchymal neoplasms, along with the appropriate use of ancillary diagnostic tests, in particular immunohistochemistry, in the evaluation of such lesions and their histological mimics.

Hyperfractionated Accelerated Reirradiation in Patients With Radiation Associated Secondary Angiosarcoma of the Breast: A Report of Local Control and Toxicity Using a Postoperative Radiation Therapy Approach

Hyperfractionated Accelerated Reirradiation in Patients With Radiation Associated Secondary Angiosarcoma of the Breast: A Report of Local Control and Toxicity Using a Postoperative Radiation Therapy Approach

Targeted massively parallel sequencing of angiosarcomas reveals frequent activation of the mitogen activated protein kinase pathway.

Angiosarcomas are rare malignant mesenchymal tumors of endothelial differentiation. The clinical behavior is usually aggressive and the prognosis for patients with advanced disease is poor with no effective therapies. The genetic bases of these tumors have been partially revealed in recent studies reporting genetic alterations such as amplifications of MYC (primarily in radiation-associated angiosarcomas), inactivating mutations in PTPRB and R707Q hotspot mutations of PLCG1. Here, we performed a comprehensive genomic analysis of 34 angiosarcomas using a clinically-approved, hybridization-based targeted next-generation sequencing assay for 341 well-established oncogenes and tumor suppressor genes. Over half of the angiosarcomas (n = 18, 53%) harbored genetic alterations affecting the MAPK pathway, involving mutations in KRAS, HRAS, NRAS, BRAF, MAPK1 and NF1, or amplifications in MAPK1/CRKL, CRAF or BRAF. The most frequently detected genetic aberrations were mutations in TP53 in 12 tumors(35%) and losses of CDKN2A in9 tumors (26%). MYC amplifications were generally mutually exclusive of TP53 alterations and CDKN2A loss and were identified in 8 tumors (24%), most of which (n = 7, 88%) arose post-irradiation. Previously reported mutations in PTPRB (n = 10, 29%) and one (3%) PLCG1 R707Q mutation were also identified. Our results demonstrate that angiosarcomas are a genetically heterogeneous group of tumors, harboring a wide range of genetic alterations. The high frequency of genetic events affecting the MAPK pathway suggests that targeted therapies inhibiting MAPK signaling may be promising therapeutic avenues in patients with advanced angiosarcomas.

Alternative lengthening of telomeres phenotype in malignant vascular tumors is highly associated with loss of ATRX expression and is frequently observed in hepatic angiosarcomas.

Alternative lengthening of telomeres (ALT) is a mechanism using homologous recombination to maintain telomere length and sustain limitless replicability of cancer cells. Recently, ALT has been found to be associated with inactivation of either α-thalassemia/mental retardation syndrome X-linked (ATRX) or death domain-associated (DAXX) protein. In this study, 119 tumors (88 angiosarcomas, 11 epithelioid hemangioendotheliomas, and 20 Kaposi sarcomas) were analyzed to determine the ALT status, its relationship to loss of ATRX/DAXX expression, and the clinicopathological features. In addition, the mutation status in the telomerase reverse transcriptase gene (TERT) promoter was also studied. Loss of ATRX expression was observed in 21% (16/77) of the primary angiosarcomas and 9% (1/11) of epithelioid hemangioendotheliomas. DAXX expression was intact in all but 2 ATRX-deficient angiosarcomas. Telomere-specific fluorescence in situ hybridization assay showed 28% (17/61) of the primary angiosarcomas were ALT positive. Remarkably, ALT was highly associated with loss of ATRX expression: all but 2 ALT-positive angiosarcomas were ATRX deficient. Notably, hepatic angiosarcomas were frequently ATRX deficient (8/13) and/or ALT positive (8/12). None of the secondary angiosarcomas were ATRX/DAXX deficient or ALT positive. The only ATRX-deficient epithelioid hemangioendothelioma was positive for ALT. Forty-seven angiosarcomas were tested for TERT promoter mutation. Despite the fact that angiosarcoma occurs most commonly in sun-damaged skin, mutation was detected in only 1 radiation-associated angiosarcoma (2%). We conclude that ALT is an important telomere maintenance mechanism in primary angiosarcomas. This feature is highly associated with loss of ATRX expression and is frequently observed in hepatic angiosarcomas.

Radiation associated angiosarcoma of the the breast treated with trimodality of surgery, radiation, and paclitaxel-based chemotherapy.

e21532 Background: Radiation associated angiosarcoma (RAAS) of the breast is rare and occurs in only 0.1-0.6% of those treated with breast conservation therapy (BCT). With resection alone there is ...

Study on early diagnosis strategy for radiation-associated breast angiosarcoma after breast cancer radiotherapy

Objective To develop an early diagnosis strategy for radiation-associated breast angiosarcoma after breast cancer radiotherapy (RABASBCR) and to avoid the misdiagnosis of this disease.Methods A systematic search of PubMed for published reports of RABASBCR cases was performed.The clinical manifestations and radiological features in the early stage of disease,as well as biopsies,were analyzed to screen out valuable markers for early diagnosis and develop the early diagnosis strategy for RABASBCR.Results Fifty-five original articles involving 80 RABASBCR patients were selected for this analysis.Twenty-four (30％) of the 80 patients were misdiagnosed;the median time of misdiagnosis was 3 months (1-24 months).The earliest symptom was skin changes in 76 (95％) of the 80 patients.The misdiagnosis rates of ultrasound,mammography,computed tomography,and magnetic resonance imaging for RABASBCR were 9/9,31/32,2/2,and 1/5,respectively.The misdiagnosis rates of fine needle biopsy,core needle biopsy,and incisional biopsy were 7/14,12/25,and 10/26,respectively.Conclusions By analyzing published case reports,we have set up the early diagnosis strategy for RABASBCR with reference to the Cahan criteria. Key words: Breast angiosarcoma; Radiotherapy-associated; Early diagnosis

Angiosarcoma primario y secundario de mama: estudio de 8 casos con evidencia de origen linfático en los angiosarcomas posradioterapia

ObjectiveTo analyze differences between primary and radiation-associated secondary breast angiosarcomas. Patients and methodsWe retrospectively reviewed all cases of angiosarcoma diagnosed at our hospital between 2000 and 2010. We analyzed the clinical and pathological features. In the immunohistochemical study, we assessed expression of CKAE1/AE3, CD31, CD34, Ki-67 and D2-40. ResultsThere were 8 women, 4 with primary angiosarcoma and 4 with secondary angiosarcoma. The mean age at presentation was 66 years for primary tumors and 74 years for secondary angiosarcomas. The mean latency period for radiation-associated angiosarcomas was 118 months. Three secondary tumors involved the skin, 3 primary angiosarcomas were intramammary and the remaining 2 were mixed. All tumors were CD31+/CD34+/CKAE1/AE3−. The secondary angiosarcomas also expressed D2-40, while the primary tumors were negative for this lymphatic marker. ConclusionsSecondary angiosarcomas express D2-40, while primary angiosarcomas are negative for this lymphatic marker. This finding suggests a lymphatic origin for post-radiation angiosarcomas.

Sporadic versus Radiation-Associated Angiosarcoma: A Comparative Clinicopathologic and Molecular Analysis of 48 Cases

Angiosarcomas are aggressive tumors of vascular endothelial origin, occurring sporadically or in association with prior radiotherapy. We compared clinicopathologic and biologic features of sporadic angiosarcomas (SA) and radiation-associated angiosarcomas (RAA). Methods. From a University of Michigan institutional database, 37 SA and 11 RAA were identified. Tissue microarrays were stained for p53, Ki-67, and hTERT. DNA was evaluated for TP53 and ATM mutations. Results. Mean latency between radiotherapy and diagnosis of RAA was 11.9 years: 6.7 years for breast RAA versus 20.9 years for nonbreast RAA (P = 0.148). Survival after diagnosis did not significantly differ between SA and RAA (P = 0.590). Patients with nonbreast RAA had shorter overall survival than patients with breast RAA (P = 0.03). The majority of SA (86.5%) and RAA (77.8%) were classified as high-grade sarcomas (P = 0.609). RAA were more likely to have well-defined vasoformative areas (55.6% versus 27%, P = 0.127). Most breast SA were parenchymal in origin (80%), while most breast RAA were cutaneous in origin (80%). TMA analysis showed p53 overexpression in 25.7% of SA and 0% RAA, high Ki-67 in 35.3% of SA and 44.4% RAA, and hTERT expression in 100% of SA and RAA. TP53 mutations were detected in 13.5% of SA and 11.1% RAA. ATM mutations were not detected in either SA or RAA. Conclusions. SA and RAA are similar in histology, immunohistochemical markers, and DNA mutation profiles and share similar prognosis. Breast RAA have a shorter latency period compared to nonbreast RAA and a significantly longer survival.

Long-Term Outcomes in Patients with Radiation-Associated Angiosarcomas of the Breast Following Surgery and Radiotherapy for Breast Cancer

Radiation-associated angiosarcoma (RAAS) is a devastating disease occasionally observed in breast cancer patients treated with radiation. Due to its rarity, our knowledge-of disease risk factors, epidemiology, treatment, and outcome-is extremely limited. Therefore, we sought to identify clinicopathologic factors associated with local and distant recurrence and disease-specific survival (DSS). Radiation-associated angiosarcoma was defined as pathologically confirmed breast or chest wall angiosarcoma arising within a previously irradiated field. A comprehensive search of our institutional tumor registry (1/1/93 through 2/28/11) was used to identify patients (n=95 females). Patient, original tumor, RAAS treatment, and outcome variables were retrospectively retrieved and assembled into a database. The median follow-up for all RAAS patients was 10.3 (range, 2.4-31.8)years. The latency period following radiation exposure ranged from 1.4 to 26 (median, 7)years. One-year and 5-year DSS rates were 93.5 and 62.6%, respectively. Reduced risk of local recurrence was observed in patients who received chemotherapy (P=0.0003). In multivariable analysis, size was found to be an independent predictor of adverse outcome (P=0.015). Our study demonstrates that RAAS exhibits high recurrence rates. It also highlights the need for well-designed, multicenter, clinical trials to inform the true utility of chemotherapy in this disease.